The importance of red flesh pigmentation for consumers, coupled with importance of understanding the evolutionary history of flesh coloration in salmonids, has led to increased interest in the molecular basis of carotenoid homeostasis. Functional genetics and biochemical characterization studies of genes involved in uptake, transport, deposition and degradation of carotenoids have advanced over the last years. Sequencing the Atlantic salmon genome has provided us with new tools like SNP-panels for GWAS-studies, detailed gene maps and access to RNA-sequencing. Emerging evidence suggest that efflux and metabolic breakdown of dietary carotenoids in small intestine significantly influence the amount of carotenoids deposed in the muscle of Atlantic salmon. Bco1/bco1l and abcg2 are key components identified so far, although a more complete understanding of the mechanisms involved in carotenoid intestinal metabolism is still lacking. Selection for genetic variants of these genes is a strategy for more intensively colored fillet in Atlantic salmon. Fig. 11 shows current view of carotenoid metabolism in Atlantic salmon in enterocyte of small intestine. However, more remains to be learned about the roles of these proteins. Future studies should also assess the substrate specificities of these proteins, and developing Atlantic salmon enterocyte cell cultures will greatly contribute to the success. Also, additional searches for flesh coloration QTLs in Atlantic salmon should be performed.
Understanding the mechanisms involved in astaxanthin binding to muscle would probably explain what is the criteria for red-flesh coloration and focus should also be set upon this topic.
Cell culture together with proteome studies will continue to contribute to improve the understanding of an interesting life history trait in Atlantic salmon.
36
Figure 11. Proposed metabolism of carotenoids in enterocyte in Atlantic salmon. Proteins studied in this thesis are colored, while other proteins supposedly involved in the pathway are non-colored. Food containing β-carotene and other typical provitamin-A carotenoids (orange spheres) and astaxanthin (red spheres) is ingested and the pigments are taken up into the enterocyte in small intestine by membrane protein transporters (Cd36, Sr-Bi, Npci-1l). Astaxanthin can be symmetrically cleaved by Bco1 into retinoids, effluxed back into the intestinal lumen through Abcg2, or remain intact. Other provitamin A carotenoids can be symmetrically cleaved by Bco1l into retinoids or remain intact. Some carotenoids can be asymmetrically cleaved into apocarotenoids by Bco2. Apocarotenoids, retinoids and intact carotenoids combine into chylomicrons (yellow spheres), which are secreted into circulation and delivered to the different tissues.
37
5. List of figures
Figure 1. Different filet colors from members of the sallmonidae family (A) Atlantic salmon (Salmo salar) (B) Rainbow trout (Oncorhynchus mykiss) (C) Sockeye salmon (Oncorhynchus nerka) and other commercial marine species (D) Atlantic halibut (Hippoglossus hippoglossus) (E) Atlantic herring (Clupea harengus) (F) Atlantic cod (Gadus morhua).
Figure 2. Chemical structures of carotenoids. The carbon-numbering scheme is shown for β-carotene. Carotenes are pure hydrocarbons and xanthophylls have oxygen groups attached (indicated in red).
Figure 3. Oxidative cleavage of β-carotene by BCO1. BCO1 cleaves provitamin-A carotenoids at the central 15,15’ double bond to yield two molecules of vitamin A aldehyde.
Figure 4. Chemical structures of optical RS isomers of astaxanthin (A) (3R, 3’R)- (B) (3R, 3’S)- (C) (3S,3’S)-astaxanthin.
Figure 5. The localization of carotenoids in biological membranes.
Figure 6. Examples of vivid coloration in different animals due to carotenoids.
Figure 7. Structural formula of astaxanthin metabolite idoxanthin. Idoxanthin is formed by reduction of the keto group in astaxanthin.
Figure 8. Variation in flesh color between two Atlantic salmon individuals.
Figure 9. Atlantic salmon with intraperitoneally injected (A) 0 and (B) 100 mg astaxanthin.
(Adapted with permission from the PhD thesis from Trine Ytrestøyl).
38
Figure 10. Schematic diagram of human ABCG2 domains showing functional single-nucleotide polymorphisms (red stars). ABCG2 is a ‘half-transporter’ presumed to homodimerize to form a functional transporter. A monomer of ABCG2 consists of intracellular N-terminal nucleotide binding domain (NBD) containing Walker A, Walker B and C-motifs that bind ATP/GTP and have catalytic function. Six membrane spanning domains (MSD), and associated intra- and extracellular loops that follow these are important for substrate binding. NBD: Nucleotide-binding domain; MSD: Membrane-spanning domain; W-A: Walker A motif; W-B: Walker B motif.
Figure 11. Proposed metabolism of carotenoids in enterocyte in Atlantic salmon. Proteins studied in this thesis are colored, while other proteins supposedly involved in the pathway are non-colored. Food containing β-carotene and other typical provitamin-A carotenoids (orange spheres) and astaxanthin (red spheres) is ingested and the pigments are taken up into the enterocyte in small intestine by membrane protein transporters (Cd36, Sr-Bi, Npci-1l).
Astaxanthin can be symmetrically cleaved by Bco1l into retinoids, effluxed back into the intestinal lumen through Abcg2, or remain intact. Other provitamin A carotenoids can be symmetrically cleaved by Bco1 into retinoids or remain intact. Some carotenoids can be asymmetrically cleaved into apocarotenoids by Bco2. Apocarotenoids, retinoids and intact carotenoids combine into chylomicrons (yellow spheres), which are secreted into circulation and delivered to the body.
39
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